Immunohistochemical Analysis of Expression of GATA3 in Carcinoma Breast and its Correlation with Prognostic Parameters

Tanvi Suri; Charanjeet Ahluwalia

doi:10.21276/apalm.3012

Tanvi Suri Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, 110029
Charanjeet Ahluwalia Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, 110029

DOI: https://doi.org/10.21276/apalm.3012

Keywords: GATA3, breast carcinoma, tumour marker, surrogate molecular classification

Abstract

Background: GATA3 plays an essential role in the normal development and function of the mammary gland where it promotes the luminal transcriptional program. Its loss is implicated in the pathogenesis of breast cancer. We proposed to study the expression of GATA3 in carcinoma breast by immunohistochemistry and determine its correlation with prognostic parameters. Methods: The expression pattern of GATA3 was evaluated by immunohistochemistry in 30 cases of invasive breast carcinoma. GATA3 scoring was done and a score of ≥ 1+ was considered positive. Patient characteristics, including age, tumour laterality, tumour size, lymph node status, tumour grade, histological type, molecular subtypes were collected. The relationships between protein expression and clinicopathological variables were analysed. Statistical significance was determined by Pearson’s chi-square test and Mann Whitney U test (for age). Result: 46.7% of cases (14/30) scored positive for GATA3 expression in tumour cells including 63% of luminal subtypes, 14% of Her-2 neu enriched carcinomas and 20% of triple negative carcinomas. Most positive cases (35.7%) demonstrated 3+ staining. GATA3 expression showed an inverse association with histological grade (P = 0.012) and HER-2 overexpression (P = 0.038), and a direct association with ER expression (P =0.017) and PR expression (P =0.009). Conclusion: GATA3 is luminal marker as it shows strong association with ER and PR in breast cancers. High GATA3 expression is also correlated good prognostic parameters like low tumour grade. Our findings advocate for GATA3 as a promising new breast-specific immunomarker.

References

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.

Malvia S, Bagadi S, Dubey U, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol. 2017;13(4):289-95.

Kouros-Mehr H, Slorach E, Sternlicht M, Werb Z. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell. 2006;127(5):1041-55.

Kouros-Mehr H, Bechis S, Slorach E, Littlepage L, Egeblad M, Ewald A et al. GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model. Cancer Cell. 2008;13(2):141-52.

Liu H, Shi J, Wilkerson ML, Lin F. Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol. 2012;138 (1):57–64.

Hoch RV, Thompson DA, Baker RJ, Weigel RJ. GATA-3 is expressed in association with estrogen receptor in breast cancer. Int J Cancer. 1999 Apr 20;84(2):122-8.

Mehra R, Varambally S, Ding L, Shen R, Sabel M, Ghosh D et al. Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis. Cancer Res. 2005;65(24):11259-64.

Yoon N, Maresh E, Shen D, Elshimali Y, Apple S, Horvath S et al. Higher levels of GATA3 predict better survival in women with breast cancer. Hum Pathol. 2010;41(12):1794-1801.

Fararjeh AS, Tu SH, Chen LC, Liu YR, Lin YK, Chang HL, et al. The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer. Hum Pathol. 2018 10;80:219-30.

Cakir A, Isik Gonul I, Ekinci O, Cetin B, Benekli M, Uluoglu O. GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas. Pathol Res Pract. 2017 Mar;213(3):227-34.

McCleskey B, Penedo T, Zhang K, Hameed O, Siegal G, Wei S. GATA3 Expression in advanced breast cancer: prognostic value and organ-specific relapse. Am J Clin Pathol. 2015;144(5):756-63.

Voduc D, Cheang M, Nielsen T. GATA-3 expression in breast cancer has a strong association with estrogen receptor but lacks independent prognostic value. Cancer Epidemiol Biomarkers Prev. 2008;17(2):365-73.

Shaoxian T, Baohua Y, Xiaoli X, Yufan C, Xiaoyu T, Hongfen L, et al. Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes. J Clin Pathol. 2017 Nov;70(11):926-34.

Demir H, Turna H, Can G, Ilvan S. Clinicopathologic and prognostic evaluation of invasive breast carcinoma molecular subtypes and GATA3 expression. J BUON. 2010;15(4):774–82.

Cimino-Mathews A, Subhawong A, Illei P, Sharma R, Halushka M, Vang R et al. GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas. Hum Pathol. 2013;44(7):1341-49.

Byrne D, Deb S, Takano E, Fox S. GATA3 expression in triple-negative breast cancers. Histopathology. 2017;71(1):63-71.

Braxton DR, Cohen C, Siddiqui MT. Utility of GATA3 immunohistochemistry for diagnosis of metastatic breast carcinoma in cytology specimens. Diagn Cytopathol. 2015 Apr;43(4):271-7.

Ciocca V, Daskalakis C, Ciocca R, Ruiz-Orrico A, Palazzo J. The significance of GATA3 expression in breast cancer: a 10-year follow-up study. Hum Pathol. 2009;40(4):489-95.

Gulbahce HE, Sweeney C, Surowiecka M, Knapp D, Varghese L, Blair CK. Significance of GATA-3 expression in outcomes of patients with breast cancer who received systemic chemotherapy and/or hormonal therapy and clinicopathologic features of GATA-3-positive tumors. Hum Pathol. 2013 Nov;44(11):2427-31.

Eeckhoute J, Keeton E, Lupien M, Krum S, Carroll J, Brown M. Positive cross-regulatory loop ties GATA-3 to estrogen receptor α expression in breast cancer. Cancer Res. 2007;67(13):6477-83.

Layton C, Bancroft JD. The hematoxylin and eosin. In: Suvarna SK, Layton C, Bancroft JD, editors. Theory and practice of histological techniques. 7th ed. Philadelphia: Elsevier; 2013. pp.179-220.

Collins LC. Breast. In: Rosai and Ackerman, editors. Surgical Pathology. 11th ed. Philadelphia: Elsevier; 2017. pp.1434-527.

Singletary SE, Allred C, Ashley P, Berry D, Bland KI, Borgen PI et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002;20:3628-36.